Molecular Epilepsy

Research Overview

The epilepsies are a common group of chronic neurological conditions that are characterised by recurrent spontaneous unprovoked epileptic seizures. Epilepsy is the second most common serious neurological disorder in the community, with approximately 9% of the population having a seizure at some stage in their lifetime and 3% developing epilepsy. A large proportion of epilepsy syndromes involve genetic alterations however the progress to date in identifying the genetic basis of epilepsy has been limited primarily to the discovery of single gene mutations that cause epilepsy in relatively rare families. For the more common types of epilepsy, it is thought that a combination of mutations in multiple genes likely determine an individual’s susceptibility to seizures, as well as the responsiveness to antiepileptic medications.

The overriding aim of the Molecular Epilepsy Group is to identify potential molecular targets that could be the basis of much more specific and effective treatments for patients who have epilepsy, and the prevention of epilepsy in those at risk.

Another area of focus for my group is centred on investigating cardiac function in animal models of epilepsy. Cardiac electrophysiological dysfunction is common in people with epilepsy; particularly in those with a longer duration of epilepsy. As a result people with epilepsy can suffer from serious cardiac arrhythmias, often precipitated by a seizure, which could contribute to their substantially increased risk of sudden death. Such deaths are termed Sudden Unexpected Death in EPilepsy (SUDEP), and this is a major clinical problem facing epilepsy patients, accounting for 17-38% of all epilepsy related deaths. Despite the high level of concern in the epilepsy community regarding cardiac dysfunction and SUDEP, and growing scientific attention into the problem, knowledge about the underlying causal mechanisms remains limited. Recent research from our laboratory has shown that heart function is detrimentally altered and the expression of ion channels critical for controlling cardiac rhythm, HCN channels, is reduced in animal models of chronic genetic and acquired epilepsy.

Understanding how chronic epilepsy results in cardiac dysfunction will allow us to develop intervention strategies to protect the heart from the adverse effects of chronic epilepsy, and thereby potentially reducing the risk of SUDEP.